Our long-term goal is to understand the signals that pattern the early vertebrate embryo, and particularly the role that BMP antagonists play in this process. During previous grant periods, we have identified a number of BMP antagonists that act in early axis formation, mesoderm patterning and neural induction. They are also essential for organogenesis. In the next grant period we will study how these antagonists act, either singly, or more frequently in overlapping combinations, in genetically modified mice. We will use mutant alleles of Noggin and Gremlin, which were both discovered and characterized by our lab, and in addition, we will use mutants of follistatin and chordin. To facilitate the recovery of mutant animals we will use conditional alleles of these genes in combination with Cre drivers. Our particular focus will be the role of the antagonists in development of the somites, gut and skeleton. PUBLIC HEALTH RELEVANCE: A variety of protein antagonists of the Bone Morphogenetic Protein signaling pathway are essential regulators of early development. They affect most organs, but are particularly known for their effects on nervous system, skeleton and stem cell development. They have current uses in stem cell culture, and considerable promise for therapies in clinical disorders such as ectopic bone deposition, all of which justifies a thorough understanding of their role in normal development of the mammalian embryo.